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Biochem > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

Function of gluconeogenesis

A

Another mechanism of maintaining blood glucose homeostasis in addition to glycogen degradation

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2
Q

When

A

FASTED state

  • Low I/G as in overnight fast
  • Prolonged exercise
  • High protein, low-carb diet
  • Stress
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3
Q

Where

A

Primary site = liver

Also in kidney to lesser extent

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4
Q

Liver cannot carry out _________

A

Glycolysis and gluconeogenesis at same time at same rate.

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5
Q

Glycolysis ___________ in the fasted state in ________

A

Decreases

the liver

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6
Q

Major non-carbohydrate precursors used as substrates (4)

A
  1. Lactate
  2. Amino acids
  3. Glycerol
  4. TCA cycle intermediates
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7
Q

All TCA cycle intermediates except ______ can be used as substrates in gluconeogenesis

A

Acetyl CoA

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8
Q

Cori Cycle =

A

Lactate recycling

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9
Q

2 functions of lactate dehydrogenase

A
  1. Maintain glycolysis during fed state (especially under anaerobic conditions) by producing NAD+
  2. Provide lactate for gluconeogenesis in fed state
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10
Q

Chemistry of forming pyruvate

Enzyme: lactate dehydrogenase

A

Oxidize -OH group on lactate to C=O —>form pyruvate

NAD+ picks up e- to NADH

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11
Q

Lactic acid produced as a consequence of anaerobic glycolysis in muscle enters blood stream —>

A

Taken up by liver —> converted to pyruvate by lactate dehydrogenase —> pyruvate serves as carbon skeletons for gluconeogenesis

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12
Q

Where does lactate come from? (2)

A
  1. RBC

2. Exercising muscle

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13
Q

Where do amino acids come from?

A

Muscle protein degradation in skeletal muscle

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14
Q

Primary amino acid used to make pyruvate?

How?

A

Alanine

Alanine aminotransferase converts to pyruvate by removing amino group

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15
Q

Where does glycerol come from?

A

Triglyceride breakdown in adipose tissue

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16
Q

Use of glycerol as a substrate

A

Glycerol + ATP —> glycerol phosphate + ADP + Pi (enzyme: glycerol kinase)
* glycerol is from stored TG here

Glycerol phosphate + NAD+ —> dihydroxyacetone phosphate + NADH

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17
Q

Dihydroxyacetone phosphate

A

A glycolytic intermediate

Generated by using glycerol from breakdown of stored triglycerides

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18
Q

_________ carbons cannot be used as substrates for gluconeogenesis

Why?

A

Fatty acid

Most FA carbons only yield acetyl CoA —> acetyl CoA through TCA cycle cannot provide for a net synthesis of sugars because 2 carbons are lost as CO2

Also pyruvate dehydrogenase reaction is irreversible

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19
Q

4 main molecules in order

A

Pyruvate —> OAA —> phosphoenolpyruvate —> glucose

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20
Q

Any ATP is coming from?

A

Oxidation of fatty acids

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21
Q

Glycolysis is shut down because?

A

Pyruvate kinase is phosphorylated and inhibited in fasted state

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22
Q

Retained steps

A

2, 4-9

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23
Q

Replaced steps

A

1, 3, 10

24
Q

Step 1

A

Pyruvate + CO2 + ATP + H2O —> OAA + ADP + Pi + 2 H+

Enzyme: pyruvate carboxylase

  • Add CO2 to pyruvate
  • Occurs in mitochondria
25
Q

Pyruvate carboxylase requires

A

Biotin as a coenzyme for carrier of CO2

Source of CO2 is bicarbonate

26
Q

What provides energy for gluconeogenesis?

A

Beta-oxidation of fatty acids

  • must happen at same time
27
Q

Allosteric activators of pyruvate carboxylase

A
  1. Acetyl-CoA : comes from FA oxidation

2. ATP

28
Q

Step 2

A

[First, OAA is transported into cytoplasm as malate and OAA is reformed.]

OAA +GTP —> Phosphoenolpyruvate + GDP + CO2

Enzyme: phosphoenolpyruvate carboxykinase (PEPCK)

29
Q

Why is GTP needed in PEPCK reaction?

A

Forming phosphoenolpyruvate which is a high energy molecule

30
Q

Energy for forming PEP is provided by:

A
  1. Hydrolyzing GTP

2. Decarboxylation is favorable (remove CO2 that pyruvate carboxylase added)

31
Q

Step 3

A

PEP + H2O 2-phosphoglycerate

32
Q

Step 4

A

2-phosphoglycerate 3-phosphoglycerate

33
Q

Step 5

A

3-phosphoglycerate + ATP 1,3-BPG + ADP

34
Q

Step 6

A

1,3-BPG + NADH Glyceraldehyde-3-phosphate + NAD+ + Pi

***Also dihydroxyacetone phosphate enters here by isomerizing to form glyceraldehyde 3-phosphate

35
Q

Step 7

A

Glycerol-3-phosphate fructose-1,6-bisphosphate

36
Q

Step 8

A

CONTROL POINT

Fructose-1,6-bisphosphate + H2O —> fructose-6-phosphate + Pi

Enzyme: Fructose-1,6-bisphosphatase
- Thermodynamically favorable

37
Q

Fructose-1,6-bisphosphate is allosterically inhibited by:

A
  1. Fructose-2,6- bisphosphate

2. AMP

38
Q

Step 9

A

Fructose-6-phosphate glucose-6-phosphate

39
Q

Step 10

A

Glucose-6–phosphate + H2O —> glucose + Pi

Enzyme: glucose-6-phosphatase

40
Q

Glucose-6-phosphatase

  • location
  • mechanism
A
  • Found in ER membrane
  • Catalytic domain faces ER lumen

Glucose-6-phosphate gets into ER lumen of liver and kidney cells —> P comes off in hydrolysis reaction —> both P and glucose exit lumen —> glucose into blood

41
Q

4 major enzymes in gluconeogenesis

A
  1. Pyruvate carboxylase
  2. PEPCK
  3. Fructose-1,6-bisphosphatase**
  4. Glucose-6-phosphatase
42
Q

3 major enzymes in glycolysis

A
  1. Pyruvate kinase
  2. PFK-1**
  3. Glucokinase / hexokinase
43
Q

PFK-1 allosteric regulation

A

Allosterically activated by F-2,6-BP and AMP

Allosterically inhibited by ATP

44
Q

Fructose-1,6-bisphosphatase allosteric regulation

A

Allosterically inhibited by F-2,6-bisphosphatase and AMP

45
Q

Pyruvate allosteric regulation

A

Activated by fructose-1,6-bisphosphate

Inhibited by ATP

46
Q

Phosphoenolpyruvate carboxykinase (PEPCK) allosteric regulation

A

Inhibited by ADP

47
Q

Pyruvate carboxylase allosteric regulation

A

Activated by acetyl CoA

Inhibited by ADP

48
Q

Glucose-6-phosphatase regulation

A

Under substrate level control

If G-6-P builds up, increase activity of enzyme

49
Q

Fructose-2,6-bisphosphatase is made by ______ in _________

A

PFK-2 (kinase domain) in fed state

50
Q

In fasted state, PFK-2 is ___________ and ________ active

Result:

A

Phosphorylated and less active

Result: Allows FBPase-2 to become more active

51
Q

In fasted state __________ degrades __________

A

FBPase-2 degrades fructose-2,6-bisphosphate

52
Q

In fed state, insulin signaling activates _________ to _________ PFK-2 to make ____________

A

In fed state, insulin signaling activates phosphoprotein phosphatase to remove phosphate from PFK-2 to make it active —> make fructose-2,6-bisphosphate

53
Q

FBPase-2 is _________ by fructose-2,6-bisphosphate

A

Inhibited

54
Q

Need _____ high energy phosphate to make 1, 6-C glucose

Where do they come from?

A

6

2 ATP in Pyruvate carboxylase reaction
2 GTP in PEPCK reaction
2 ATP as 2 moles of 3-phosphoglycerate —> 2 mol 1,3-BPG

55
Q

ATP in fasted state

A

NOT limited

Why? —> Fatty acids give more ATP than glucose

56
Q

Glycolysis = ________ energy

Gluconeogenesis = _________ energy

A

Glycolysis releases energy (ATP and NADH)

Gluconeogenesis consumes ATP and NADH

57
Q

Glycolysis and gluconeogenesis are ________ regulated.

A

Reciprocally

Biochem (15 decks)

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